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November 13, 2025
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Early Access
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Site-Selective Peptide and Protein Functionalization with Cyclopropenium Cations

Publicated to: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (): - - 2025-11-04 (), DOI: 10.1002/anie.202518939

Authors: Faraone, Adriana; Balletti, Matteo; Jeandin, Alienor; Tu, Hang-fei; Ikonnikova, Viktoria A; Sojka, Laura S; Suero, Marcos G

Affiliations

Barcelona Inst Sci & Technol, Inst Chem Res Catalonia ICIQ CERCA, Ave Paisos Catalans 16, Tarragona 43007, Spain - Author
ICREA, Pg Lluis Companys 23, Barcelona 08010, Spain - Author

Abstract

In the realm of organic chemistry, carbocations play a pivotal role as highly reactive intermediates in the synthesis of complex molecules. While cyclase enzymes construct terpenoid natural products through carbocation intermediates, the use of these electrophilic reactive species for peptide and protein bioconjugation in aqueous media remains unexplored. Herein, we disclose the discovery and development of a new chemical modification of peptides and proteins with aromatic cyclopropenium cations, selective at cysteine residues. The bioconjugation is fast, operationally simple, and occurs at low concentration in aqueous media, allowing for the installation of a tetrasubstituted cyclopropene ring with excellent site selectivity. Moreover, the cyclopropenylation is preferential to internal cysteines, thus complementing current methodologies for selective terminal cysteine bioconjugation. These studies further showcased the bioconjugates' utility as radical traps in a thiol-ene process, enabling the formation of cyclopropane-linked conjugates.

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal ANGEWANDTE CHEMIE-INTERNATIONAL EDITION due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 15/239, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-17:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 1.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 1 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Faraone, Adriana) and Last Author (Suero, Marcos G).

the author responsible for correspondence tasks has been Suero, Marcos G.

Awards linked to the item

The European Research Council (ERC-CoG 2019, 865554), the Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU/AEI/10.13039/501100011033): PID2022-140286NB-I00 (FEDER-EU), the Severo Ochoa Excellence Accreditation (CEX2019-000925-S, CEX2024-001469-S), the ICIQ Foundation, the ICREA Foundation, and the CERCA Programme are gratefully acknowledged for financial support. The authors especially thank ICIQ for the ICIQ-Severo Ochoa Strategic Funds Call and the European Union for a Marie Sk & lstrok;odowska-Curie Individual Fellowship (101032589 to H.-F.T.).